High-flow nasal cannula for severe COVID-19 patients in a Japanese single-center, retrospective, observational study: 1 year of clinical experience.

High-flow nasal cannula (HFNC) can be effective in treating type 1 respiratory failure by reducing the severity of coronavirus disease 2019 (COVID-19). The purpose of this study was to assess the reduction of disease severity and safety of HFNC treatment in patients with severe COVID-19. We retrospectively observed 513 consecutive patients with COVID-19 admitted to our hospital from January 2020 to January 2021. We included patients with severe COVID-19 who received HFNC for their deteriorating respiratory status. HFNC success was defined as improvement in respiratory status after HFNC and transfer to conventional oxygen therapy, while HFNC failure was defined as transfer to non-invasive positive pressure ventilation or ventilator, or death after HFNC. Predictive factors associated with failure to prevent severe disease were identified. Thirty-eight patients received HFNC. Twenty-five (65.8%) patients were classified in the HFNC success group. In the univariate analysis, age, history of chronic kidney disease (CKD), non-respiratory sequential organ failure assessment (SOFA) ≥ 1, oxygen saturation to fraction of inspired oxygen ratio (SpO2/FiO2) before HFNC ≤ 169.2, were significant predictors of HFNC failure. Multivariate analysis revealed that SpO2/FiO2 value before HFNC ≤ 169.2 was an independent predictor of HFNC failure. No apparent nosocomial infection occurred during the study period. Appropriate use of HFNC for acute respiratory failure caused by COVID-19 can reduce the severity of severe disease without causing nosocomial infection. Age, history of CKD, non-respiratory SOFA before HFNC ≤ 1, and SpO2/FiO2 before HFNC ≤ 169.2 were associated with HFNC failure.

Efficacy and safety of sotrovimab for vaccinated or unvaccinated patients with mild-to-moderate COVID-19 in the omicron era.

Although sotrovimab, one of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibodies has been shown to be effective in patients with mild-to-moderate coronavirus disease 2019 (COVID-19) with risk factors, their efficacy in mRNA COVID-19 vaccinated patients in omicron era is unknown. To evaluate the effectiveness of sotrovimab clinical data from both COVID-19 vaccinated and unvaccinated patients who were hospitalized and receiving sotrovimab at the Japanese Red Cross Medical Center were compared. The efficacy and adverse events were evaluated. Of the total 60 patients enrolled in this study, 45 had received the mRNA COVID-19 vaccine and 15 were unvaccinated. The clinical progression with low nasal cannula or face mask was not significantly different between groups (occurring in one patient in each group; p = 0.44), with no further progression in both groups. The duration of hospitalization was eight days for both groups (p = 0.90). Two patients in each group experienced adverse events (7%, p = 0.26). The results suggested that the efficacy and safety of sotrovimab against mild-to-moderate COVID-19 with risk factors in the omicron era might not be different regardless of the vaccination status. The results of the present study are encouraging; however, further randomized clinical studies are needed.

Clinical outcomes of corticosteroids for COVID-19 patients at the National Center for Global Health and Medicine during the first wave of infections.

BACKGROUND: Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2, has been a significant concern worldwide since its outbreak in December 2019. Various treatments are being researched and developed, and there are reports that dexamethasone has reduced the mortality rate and improved the clinical course of critically ill patients with COVID-19. In this study, we examined the clinical efficacy of corticosteroid therapy for patients with COVID-19 in our hospital during the first wave of infections. METHODS: We retrospectively reviewed the medical records of patients with COVID-19 who were treated with or without corticosteroid therapy at the National Center for Global Health and Medicine in Japan between February and April 2020. The primary outcome was improvement in the patients' clinical course using a seven-category ordinal scale. We collected data on patient characteristics, treatment, and clinical course, and compared them between two groups: the steroid-using group and the non-steroid-using group. RESULTS: Between February and April 2020, 110 patients were diagnosed with COVID-19. Despite poor conditions during admission into the steroid group, there were no statistical differences in clinical course between both groups, as measured using the scale. There were no statistical differences between the two groups in the number of days to fever resolution or negative polymerase chain reaction results. CONCLUSIONS: There was no difference in the clinical course between both groups. Because of the difference in background, corticosteroids may potentially make the clinical course of severely ill patients similar to that of mildly ill patients.

Clinical impact of combination therapy with baricitinib, remdesivir, and dexamethasone in patients with severe COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread worldwide and is also an important disease in Japan. Thus, the optimal treatment strategy for severe COVID-19 should be established urgently. The effects of combination treatment with baricitinib-a Janus kinase inhibitor, remdesivir, and dexamethasone (BRD) are unknown. METHODS: Patients who received combination therapy with BRD at the Japanese Red Cross Medical Center were enrolled in the study. All patients received baricitinib (≤14 d), remdesivir (≤10 d), and dexamethasone (≤10 d). The efficacy and adverse events were evaluated. RESULTS: In total, 44 patients with severe COVID-19 were enrolled in this study. The 28-d mortality rate was low at 2.3% (1/44 patients). The need for invasive mechanical ventilation was avoided in most patients (90%, 17/19 patients). Patients who received BRD therapy had a median hospitalization duration of 11 d, time to recovery of 9 d, duration of intensive care unit stay of 6 d, duration of invasive mechanical ventilation of 5 d, and duration of supplemental oxygen therapy of 5 d. Adverse events occurred in 15 patients (34%). Liver dysfunction, thrombosis, iliopsoas hematoma, renal dysfunction, ventilator-associated pneumonia, infective endocarditis, and herpes zoster occurred in 11%, 11%, 2%, 2%, 2%, 2%, and 2% of patients, respectively. CONCLUSIONS: Combination therapy with BRD was effective in treating severe COVID-19, and the incidence rate of adverse events was low. The results of the present study are encouraging; however, further randomized clinical studies are needed.

A Kidney Transplant Patient Who Died of COVID-19-associated Severe Acute Respiratory Distress Syndrome.

We herein report a 67-year-old kidney transplant patient who died of COVID-19. He was treated with hydroxychloroquine and azithromycin and received mechanical ventilation that temporarily improved his respiratory status. Despite our efforts, however, he later developed respiratory failure and died 43 days after the disease onset. The autopsy revealed prominent organization of alveoli and alveolar ducts, with a massive accumulation of macrophages in the lungs. A few severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen-positive cells were detected in the lung, suggesting delayed virus clearance owing to his long-term immunosuppressed state, leading to constant lung damage and ultimately respiratory failure.

Side effects and antibody titer transition of the BNT162b2 messenger ribonucleic acid coronavirus disease 2019 vaccine in Japan.

BACKGROUND: The coronavirus disease (COVID-19) has afflicted large populations worldwide. Although vaccines aroused great expectations, their side effects on Japanese people and the antibody titer transition after vaccination are unclear. METHODS: The side effects of the BNT162b2 mRNA COVID-19 vaccine in participants who received vaccination at our center were investigated. Some participants were also surveyed for the antibody titer transition. RESULTS: In this study, 983 and 798 Japanese participants responded to the first and second doses, respectively. Side effects occurred in 757 (77.0%) and 715 participants (90.0%) after the first and second doses, respectively. No Grade 4 side effects occurred. The second dose had significantly more side effects than the first dose (p < 0.001). Side effects occurred after the second dose in 571 female (92.1%) and 178 male participants (80.1%). Female participants had a higher incidence of side effects than the male participants (p < 0.001). A comparison among the age groups showed significant differences (p = 0.018), and the frequency of side effects decreased with age. Twenty-three individuals participated in the survey of antibody titer transition. After the second vaccine dose, the median antibody titers for IgG and IgM were 3.76 and 0.07 AU/mL, respectively. Both IgG and IgM titers showed a significant increase over the study period (p < 0.001). CONCLUSIONS: The BNT162b2 mRNA COVID-19 vaccine might be safe for Japanese people, and the antibody titer increased with two doses of vaccination. Larger nationwide studies are warranted to verify these findings.

Corticosteroids for hospitalized patients with mild to critically-ill COVID-19: a multicenter, retrospective, propensity score-matched study.

Corticosteroids use in coronavirus disease 2019 (COVID-19) is controversial, especially in mild to severe patients who do not require invasive/noninvasive ventilation. Moreover, many factors remain unclear regarding the appropriate use of corticosteroids for COVID-19. In this context, this multicenter, retrospective, propensity score-matched study was launched to evaluate the efficacy of systemic corticosteroid administration for hospitalized patients with COVID-19 ranging in the degree of severity from mild to critically-ill disease. This multicenter, retrospective study enrolled consecutive hospitalized COVID-19 patients diagnosed January-April 2020 across 30 institutions in Japan. Clinical outcomes were compared for COVID-19 patients who received or did not receive corticosteroids, after adjusting for propensity scores. The primary endpoint was the odds ratio (OR) for improvement on a 7-point ordinal score on Day 15. Of 1092 COVID-19 patients analyzed, 118 patients were assigned to either the corticosteroid and non-corticosteroid group, after propensity score matching. At baseline, most patients did not require invasive/noninvasive ventilation (85.6% corticosteroid group vs. 89.8% non-corticosteroid group). The odds of improvement in a 7-point ordinal score on Day 15 was significantly lower for the corticosteroid versus non-corticosteroid group (OR, 0.611; 95% confidence interval [CI], 0.388-0.962; p = 0.034). The time to improvement in radiological findings was significantly shorter in the corticosteroid versus non-corticosteroid group (hazard ratio [HR], 1.758; 95% CI, 1.323-2.337; p < 0.001), regardless of baseline clinical status. The duration of invasive mechanical ventilation was shorter in corticosteroid versus non-corticosteroid group (HR, 1.466; 95% CI, 0.841-2.554; p = 0.177). Of the 106 patients who received methylprednisolone, the duration of invasive mechanical ventilation was significantly shorter in the pulse/semi-pulse versus standard dose group (HR, 2.831; 95% CI, 1.347-5.950; p = 0.006). In conclusion, corticosteroids for hospitalized patients with COVID-19 did not improve clinical status on Day 15, but reduced the time to improvement in radiological findings for all patients regardless of disease severity and also reduced the duration of invasive mechanical ventilation in patients who required intubation.Trial registration: This study was registered in the University hospital Medical Information Network Clinical Trials Registry on April 21, 2020 (ID: UMIN000040211).

Diagnostic accuracy of nasopharyngeal swab, nasal swab and saliva swab samples for the detection of SARS-CoV-2 using RT-PCR.

BACKGROUND: The current gold standard in coronavirus disease (COVID-19) diagnostics is the real-time reverse transcription-polymerase chain reaction (RT-PCR) assay for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in nasopharyngeal swab (NPS) samples. Alternatively, nasal swab (NS) or saliva swab (SS) specimens are used, although available data on test accuracy are limited. We examined the diagnostic accuracy of NPS/NS/SS samples for this purpose. METHODS: Ten patients were included after being tested positive for SARS-CoV-2 RT-PCR in NPS samples according to the National Institute of Infectious Disease guidelines. In comparison with this conventional diagnostic method, NPS/NS/SS samples were tested using the cobas 6800 systems RT-PCR device. To investigate the usefulness of the cobas method and the difference among sample types, the agreement and sensitivity were calculated. Five to six samples were collected over a total period of 5-6 d from each patient. RESULTS: Fifty-seven sets of NPS/NS/SS samples were collected, of which 40 tested positive for COVID-19 by the conventional method. Overall, the concordance rates using the conventional method were 86.0%/70.2%/54.4% for NPS/NS/SS samples (cobas); however, for samples collected up to and including on Day 9 after disease onset (22 negative and one positive specimens), the corresponding rates were 95.7%/87.0%/65.2%. The overall sensitivity estimates were 100.0%/67.5%/37.5% for NPS/NS/SS samples (cobas). For samples up to 9 d after onset, the corresponding values were 100.0%/86.4%/63.6%. CONCLUSIONS: NS samples are more reliable than SS samples and can be an alternative to NPS samples. They can be a useful diagnostic method in the future.

Sustained coronavirus disease 2019-related organizing pneumonia successfully treated with corticosteroid.

A 70-year-old Japanese man contracted severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and required oxygen to maintain oxygen saturation (>90%), 5 weeks after onset of coronavirus disease 2019 (COVID-19) symptoms. Transbronchial lung cryobiopsy revealed pathological features of organizing pneumonia with alveolar epithelial injury, and prednisolone administration led to alleviation of respiratory symptoms and recovery of respiratory function. This case report is the first to demonstrate the use of corticosteroids to successfully treat post-COVID-19 respiratory failure in a patient with biopsy-proven organizing pneumonia. We propose that steroid treatment be considered for patients with persistent respiratory dysfunction as COVID-19 pneumonia sequelae.

Direct hemoperfusion using a polymyxin B-immobilized polystyrene column for COVID-19.

OBJECTIVE: To evaluate the efficacy and safety of direct hemoperfusion using a polymyxin B-immobilized polystyrene column (PMX-DHP) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive pneumonia patients. METHODS: This study was a case series conducted at a designated infectious diseases hospital. Twelve SARS-CoV-2-positive patients with partial pressure of arterial oxygen/percentage of inspired oxygen (P/F) ratio < 300 were treated with PMX-DHP on two consecutive days each during hospitalization. We defined day 1 as the first day when PMX-DHP was performed. PMX-DHP efficacy was assessed on days 7 and 14 after the first treatment based on eight categories. Subsequently, improvement in P/F ratio and urinary biomarkers on days 4 and 8, malfunctions, and ventilator and extracorporeal membrane oxygenation avoidance rates were also evaluated. RESULTS: On day 14 after the first treatment, disease severity decreased in 58.3% of the patients. P/F ratio increased while urine ß2-microglobulin decreased on days 4 and 8. Cytokine measurement pre- and post-PMX-DHP revealed decreased levels of interleukin-6 and the factors involved in vascular endothelial injury, including vascular endothelial growth factor. Twenty-two PMX-DHPs were performed, of which seven and five PMX-DHPs led to increased inlet pressure and membrane coagulation, respectively. When the membranes coagulated, the circuitry needed to be reconfigured. Circuit problems were usually observed when D-dimer and fibrin degradation product levels were high before PMX-DHP. CONCLUSIONS: Future studies are expected to determine the therapeutic effect of PMX-DHP on COVID-19. Because of the relatively high risk of circuit coagulation, coagulation capacity should be assessed beforehand.

Successful Recovery from COVID-19-associated Acute Respiratory Failure with Polymyxin B-immobilized Fiber Column-direct Hemoperfusion.

An 83-year-old man was hospitalized for coronavirus disease 2019 (COVID-19) after a 10-day history of a persistent fever. Chest computed tomography showed extensive non-segmental ground glass opacity. Despite the initiation of lopinavir and ritonavir, respiratory failure progressed. Two days of polymyxin B-immobilized fiber column-direct hemoperfusion (PMX-DHP) with adjunctive corticosteroid prevented his respiratory condition from worsening. For rapidly progressive COVID-19 cases, the early use of PMX-DHP may avoid the need for mechanical ventilation by suppressing local inflammation of the lung.

Psychiatric burdens or stress during hospitalization and concerns after discharge in patients with severe acute respiratory syndrome coronavirus-2 isolated in a tertiary care hospital.

•Quarantined inpatients with SARS-CoV-2 have psychiatric burdens.•Some inpatients had discrimination, prejudice, and suspension and dismissal from work.•Implementation of necessary measures is needed to minimize the risk of long-term social isolation and potential risk of suicide.